The exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides to initiate the up- or down-regulation of ClpCP activity. We also examine exciting recent forays into BacPROTACs to trigger the degradation of specific proteins of interest through the hijacking of the ClpCP machinery. These strategies represent an important emerging avenue for combatting antimicrobial resistance.

中文翻译：

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针对细菌降解机制作为抗菌策略

利用细胞的自然降解机制进行治疗是细菌方面一个处于起步阶段的令人兴奋的研究领域。在这里，我们回顾了当前针对 ClpCP 系统的策略，该系统是一种蛋白水解降解复合物，对于许多具有科学意义的细菌物种的生物学至关重要。策略包括使用天然产物抗生素或酰基缩肽来启动 ClpCP 活性的上调或下调。我们还研究了最近对 BacPROTAC 的令人兴奋的尝试，通过劫持 ClpCP 机制来触发特定目标蛋白质的降解。这些策略代表了对抗抗菌素耐药性的重要新兴途径。